Non-inferiority Trial on Treatments in Early COVID-19

Summary

The study aims at assessing the non-inferiority of tixagevimab plus cilgavimab and nirmatrelvir plus ritornavir vs. sotrovimab (reference standard due to the wider evidence gathered on its efficacy) on COVID-19 progression in a real-life setting of outpatients aged at least 50 years at an early stage of the disease. The progression of COVID-19 disease (hospitalization, need for supplementary oxygen therapy at home, death) within 14 days of randomisation is the composite outcome variable on which the calculation of the sample size is based. Based on available data regarding the reduction in the number of hospitalisations and medical visits with the use of sotrovimab at an early-stage of COVID-19, a disease progression of 1% has been estimated in the reference arm. 3% delta margin was considered clinically relevant, taking into account both the estimates of disease progression in the study population in absence of early treatment (7%, based on national data) and the efficacy of the reference standard. Therefore, 1095 participants will be randomly assigned in an equal ratio between the reference standard and each of the other two experimental arms (1:1:1). Randomization will be computer-generated in permuted blocks with a stratification based on site.

Timeline

Start

2022-03-07

Primary completion

2023-10-29

Completion

2023-10-29

Publications

• Mazzotta V, Mazzaferri F, Lanini S, Mirandola M, Cozzi Lepri A, Vergori A, Savoldi A, Santoro A, Maccarrone G, Mastrorosa I, Simonetti O, Zottis F, Nicastri E, Rosini G, Rovigo L, Tavernaro L, Sarmati L, Tascini C, Girardi E, Cattelan AM, Antinori A, Tacconelli E; MANTICO2/MONET study group. Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves. J Infect. 2024 Nov;89(5):106294. doi: 10.1016/j.jinf.2024.106294. Epub 2024 Sep 27.

Drugs

Indications